The proposed research has as its ultimate goals the development of new, potentially more effective and selective, anticonvulsant agents for use in the treatment of epilepsy, and elucidation of the processes involved in their action. We propose to approach these goals through the design and synthesis of novel classes of inhibitors of the pyridoxal phosphate-dependent enzyme GABA transaminase. Inhibitors of both the irreversible, "suicide" type and the competitive type will be investigated. Gamma-Aminobutyric acid (GABA) is generally recognized as a primary inhibitory neurotransmitter in the brain. A considerable body of evidence suggests the involvement of deficient brain GABA levels in the induction of epileptic seizures and elevation of GABA levels has been shown to block experimental seizures. GABA transaminase, which is the primary enzyme involved in its metabolic destruction. A search for selective inhibitors of GABA transaminase appears to offer significant promise of leading to useful agents for the selective control of epileptic disorders. We propose to: a) synthesize compounds designed to inhibit GABA transaminase selectively, either competitively or irreversiby via a suicide mechanism, and to be capable of entering the brain from the systemic circulation; and b) submit the synthesized compounds to NINCDS for pharmacologic screening. The work may contribute to: a) further understanding of the mechanisms involved in the inhibition of GABA transaminase; b) increased understanding of the processes involved in the induction of epileptic seizures; and c) the ultimate development of potentially useful drugs.